Rikkunshito ameliorates cachexia associated with bleomycin-induced lung fibrosis in mice by stimulating ghrelin secretion

Cachexia is a frequent complication in patients with respiratory failure, such as lung Received 2 May 2014 fibrosis, and it is a determining factor for functional capacity, health status, and mortality. Revised 30 July 2014 Reductions in body weight and skeletal muscle mass are key features of cachexia that are Accepted 27 August 2014 resistant to current therapies. Rikkunshito (RKT), a traditional Japanese herbal medicine, is widely used for the treatment for patients with gastrointestinal symptoms and known to Keywords: stimulate ghrelin secretion. By using bleomycin (BLM)-induced lung fibrosis mice in this Rikkunshito study, we tested our hypothesis that RKT administration could ameliorate pulmonary Cachexia cachexia. After BLM administration, mice were provided with either RKT or distilled water Ghrelin on a daily basis. Compared with the BLM-injected mice, the RKT-treated mice had smaller Lung fibrosis reductions of food intake and body weight. Skeletal muscle weights were retained in the Bleomycin RKT-treated mice, in conjunction with reduced expressions of MuRF-1 and atrogin-1 in the Mice lysates of skeletal muscle found in lung fibrosis. Rikkunshito administration restored the plasma concentrations of ghrelin in BLM-injected mice. The anticachectic efficacies of RKT administration in BLM-injected mice were canceled by the concurrent treatment of a ghrelin receptor antagonist. Rikkunshito administration did not decrease the degree of loss of body weight or food intake reduction in either ghrelin-deficient mice or growth hormone secretagogue receptor-deficient mice. Our results indicate that RKT administration exerts protective effects on pulmonary cachexia by ameliorating skeletal muscle wasting and food intake reduction as mediated by the ghrelin system and, thus, highlight RKT as a potential therapeutic agent for the management of lung fibrosis. (C) 2014 Elsevier Inc. All rights reserved.